Melatonin regulates mitochondrial dynamics and mitophagy: Cardiovascular protection

J Cell Mol Med. 2024 Sep;28(18):e70074. doi: 10.1111/jcmm.70074.

Abstract

Despite extensive progress in the knowledge and understanding of cardiovascular diseases and significant advances in pharmacological treatments and procedural interventions, cardiovascular diseases (CVD) remain the leading cause of death globally. Mitochondrial dynamics refers to the repetitive cycle of fission and fusion of the mitochondrial network. Fission and fusion balance regulate mitochondrial shape and influence physiology, quality and homeostasis. Mitophagy is a process that eliminates aberrant mitochondria. Melatonin (Mel) is a pineal-synthesized hormone with a range of pharmacological properties. Numerous nonclinical trials have demonstrated that Mel provides cardioprotection against ischemia/reperfusion, cardiomyopathies, atherosclerosis and cardiotoxicity. Recently, interest has grown in how mitochondrial dynamics contribute to melatonin cardioprotective effects. This review assesses the literature on the protective effects of Mel against CVD via the regulation of mitochondrial dynamics and mitophagy in both in-vivo and in-vitro studies. The signalling pathways underlying its cardioprotective effects were reviewed. Mel modulated mitochondrial dynamics and mitophagy proteins by upregulation of mitofusin, inhibition of DRP1 and regulation of mitophagy-related proteins. The evidence supports a significant role of Mel in mitochondrial dynamics and mitophagy quality control in CVD.

Keywords: cardiovascular disease; dynamin‐related protein 1; heart; melatonin; mitochondrial fission; mitochondrial fusion; mitophagy.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiotonic Agents / pharmacology
  • Cardiovascular Diseases* / metabolism
  • Cardiovascular Diseases* / pathology
  • Cardiovascular Diseases* / prevention & control
  • Humans
  • Melatonin* / pharmacology
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondrial Dynamics* / drug effects
  • Mitophagy* / drug effects
  • Signal Transduction / drug effects

Substances

  • Melatonin
  • Cardiotonic Agents